H1N1 Influenza Virus-like Particles: Physical Degradation Pathways and Identification of Stabilizers
H1N1 Influenza Virus-like Particles: Physical Degradation Pathways and Identification of Stabilizers
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DOI：
10.1002/jps.22304
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发表时间：
2011-02-01
影响因子：
3.8
通讯作者：
Middaugh, C. Russell
中科院分区：
文献类型：
--
作者：
Kissmann, Julian;Joshi, Sangeeta B.;Middaugh, C. Russell
一种简单而快速的疫苗稳定化方法已被应用于一种新的病毒样颗粒（VLP），其中含有主要的流感抗原（血凝素和神经氨酸酶表面蛋白）。使用光谱和光散射技术的补充来表征流感VLP的物理稳定性作为温度和pH（两种药学相关的应激因素）的函数。所得的数据集被数学转换成三色经验相图（EPD），说明了物理状态的变化作为这些应力因素的函数。然后使用对应于EPD中的表观相界的温度和pH条件从通常被认为是安全的化合物的库中筛选VLP聚集的抑制剂。鉴定了几种有效的VLP聚集抑制剂;其中，发现海藻糖、山梨醇和甘氨酸均对病毒蛋白三级结构和/或膜完整性产生显著的稳定作用。(C)2010 Wiley-Liss，Inc.和American Pharmacologist Association J Pharm Sci 100：634-645，2011
A simple and rapid approach to vaccine stabilization has been applied to a novel virus-like particle (VLP) that contains the primary influenza antigens (hemagglutinin and neuraminidase surface proteins). A complement of spectroscopic and light scattering techniques was used to characterize the physical stability of influenza VLPs as a function of temperature and pH, two pharmaceutically relevant stress factors. The resulting data set was mathematically converted into a three-color empirical phase diagram (EPD) that illustrates changes in physical state as a function of these stress factors. Conditions of temperature and pH corresponding to apparent phase boundaries in the EPD were then used to screen for inhibitors of VLP aggregation from a library of generally recognized as safe compounds. Several potent inhibitors of VLP aggregation were identified; of these, trehalose, sorbitol, and glycine were all found to exert significant stabilizing effects on viral protein tertiary structure and/or membrane integrity. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:634-645, 2011